Background: The pharmacological application of kaempferol, a natural flavonol present in different plant species, has been demonstrated to have extensive anti-inflammatory, anti-apoptotic, anti-oxidative, and anti-cancer effects. Pyroptosis is an inflammatory form of programed cell death by membranolysis and associated leakage of cytoplasm. This study investigated the molecular mechanism of kaempferol-induced effects on the pyroptosis in splenic lymphocytes (SLCs) isolated from mice. Methods: Lipopolysaccharide (LPS)-primed and adenosine triphosphate (ATP)-stimulated SLCs were used to establish the pyroptosis model. The kaempferol pretreatment was tested in the model. Results: The results show that kaempferol alleviates LPS-ATP mediated damage by increasing cell viability, improving membrane integrity, and decreasing the release of IL1b and IL-18. Kaempferol reduces pyroptosis by suppressing the expression and activity of caspase-1, increasing the protein expression of Toll-like receptor 4 (TLR4) and NOD-like receptor 3 (NLRP3), and inhibition of the decomposition of gasdermin D (GSDMD). Conclusions: Our data suggest that kaempferol exhibits anti-pyroptosis activities, which warrants further detailed investigation.
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